血清中MMP-2和MMP-9与乳头状甲状腺癌的关系

目的 探讨基质金属蛋白酶 2 (MMP-2) 及基质金属蛋白酶 9 (MMP-9) 与乳头状甲状腺癌的关系.方法 采用酶联免疫吸附法测定30例健康对照组和30例甲状腺良性结节患者及23例乳头状甲状腺癌患者血清中的MMP-2和MMP-9的水平,分析其与乳头状甲状腺癌之间的关系.结果 乳头状甲状腺癌组血清中MMP-2、MMP-9的水平显著高于甲状腺良性结节患者组和健康对照组(P＜0.01).甲状腺良性结节患者组和健康对照组之间差异无统计学意义(P＞0.05).结论 血清中MMP-2、MMP-9水平的检测对乳头状甲状腺癌患者有重要的临床意义,可作为甲状腺患者手术前的重要评估方法.     

银杏叶提取物对糖尿病大鼠肾脏基质金属蛋白酶2表达的影响

目的 观察银杏叶提取物(GbE)对雄性SD糖尿病大鼠肾脏基质金属蛋白酶2(MMP-2)和Ⅳ型胶原表达的影响,从而探讨银杏叶对糖尿病肾病的保护机制.方法 24只链脲佐菌素诱导的SD大鼠完全随机分成糖尿病对照组(DM组)和GbE组,并以12只正常雄性SD大鼠作为正常对照组(NC组).分别于4、8周后,观察各组大鼠体重、肾重、随机血糖、尿蛋白排泄率等生化指标,并用免疫组化和逆转录聚合酶链反应方法 观察糖尿病大鼠肾脏MMP-2及Ⅳ型胶原的表达.结果 糖尿病大鼠的随机血糖、体重、肾脏/体重明显下降,尿白蛋白排泄率明显升高[DM组(31.59±4.59)mg/24 h比NC组(8.74±2.08)mg/24 h,P＜0.05],GbE组糖尿病大鼠尿白蛋白排泄率[(21.38±3.86)mg/24 h]较DM组有所下降(P＜0.05).8周时,与正常对照组相比,DM组大鼠肾小球MMP-2蛋白的表达水平明显下降[(0.49±0.07)mg/24 h比(0.15±0.04)mg/24 h,P＜0.05],而GbE组DM组大鼠肾小球MMP-2蛋白的表达水平[(0.48±0.07)mg/24 h]较DM组无明显下降(P＞0.05);DM组大鼠Ⅳ型胶原的表达水平较NC组明显升高[(3.48±0.54)mg/24h比(1.68±0.51)mg/24 h],而GbE组糖尿病大鼠较NC组无明显升高[(2.55±0.50)mg/24 h比(1.68±0.51)mg/24 h].结论 GbE可通过抑制糖尿病大鼠MMP-2过表达,进而对糖尿病肾病发挥保护作用.

Abstract：

Objective To study the effect of ginkgo biloba extract (GbE) on the expression of matrix metalloproteinase (MMP)-2 in kidneys of diabetic rates and to analyze the protecting mechanism of GbE on diabetic nephropathy. Methods Totally 24 SD rats of diabetic nephropathy induced by streptozotocin were randomly divided into two groups: diabetes group and treatment group with GbE, and 12 rats with placebo therapy were enrolled as the normal control group. Rats were killed after 4 ～ 8 weeks treatment and the expression of MMP-2 and type Ⅳ collagen were studies by immunohistochemistry and RT-PCR. Results In diabetic rats, blood sugar, weight and kidney/body weight ratio were decreased significantly and the excretion of 24 hour urinary protein was increased significantly compared to the diabetes group. But the excretion of 24 hour urinary protein was improved in GbE group ( P ＜0.05 ). The expression level of MMP-2 protein and mRNA was decreased significantly in renal glomduri of diabetic rats ( P ＜ 0.05 ) but showed no changes in GbE treatment group compared to diabetes group( P ＞ 0.05 ). The expression level of type Ⅳ collagen was significantly increased in diabetic rats( P ＜0.05 ) but showed no changes in GbE group( P ＞0.05). Conclusion GbE can improve diabetic nephropathy by inhibiting the expression of MMP-2 in diabetic Rat.     

银杏叶提取物对糖尿病大鼠肾脏基质金属蛋白酶2表达的影响

Objective To study the effect of ginkgo biloba extract (GbE) on the expression of matrix metalloproteinase (MMP)-2 in kidneys of diabetic rates and to analyze the protecting mechanism of GbE on diabetic nephropathy. Methods Totally 24 SD rats of diabetic nephropathy induced by streptozotocin were randomly divided into two groups: diabetes group and treatment group with GbE, and 12 rats with placebo therapy were enrolled as the normal control group. Rats were killed after 4 ～ 8 weeks treatment and the expression of MMP-2 and type Ⅳ collagen were studies by immunohistochemistry and RT-PCR. Results In diabetic rats, blood sugar, weight and kidney/body weight ratio were decreased significantly and the excretion of 24 hour urinary protein was increased significantly compared to the diabetes group. But the excretion of 24 hour urinary protein was improved in GbE group ( P ＜0.05 ). The expression level of MMP-2 protein and mRNA was decreased significantly in renal glomduri of diabetic rats ( P ＜ 0.05 ) but showed no changes in GbE treatment group compared to diabetes group( P ＞ 0.05 ). The expression level of type Ⅳ collagen was significantly increased in diabetic rats( P ＜0.05 ) but showed no changes in GbE group( P ＞0.05). Conclusion GbE can improve diabetic nephropathy by inhibiting the expression of MMP-2 in diabetic Rat.     

银杏叶提取物对糖尿病大鼠肾脏基质金属蛋白酶2表达的影响

Objective To study the effect of ginkgo biloba extract (GbE) on the expression of matrix metalloproteinase (MMP)-2 in kidneys of diabetic rates and to analyze the protecting mechanism of GbE on diabetic nephropathy. Methods Totally 24 SD rats of diabetic nephropathy induced by streptozotocin were randomly divided into two groups: diabetes group and treatment group with GbE, and 12 rats with placebo therapy were enrolled as the normal control group. Rats were killed after 4 ～ 8 weeks treatment and the expression of MMP-2 and type Ⅳ collagen were studies by immunohistochemistry and RT-PCR. Results In diabetic rats, blood sugar, weight and kidney/body weight ratio were decreased significantly and the excretion of 24 hour urinary protein was increased significantly compared to the diabetes group. But the excretion of 24 hour urinary protein was improved in GbE group ( P ＜0.05 ). The expression level of MMP-2 protein and mRNA was decreased significantly in renal glomduri of diabetic rats ( P ＜ 0.05 ) but showed no changes in GbE treatment group compared to diabetes group( P ＞ 0.05 ). The expression level of type Ⅳ collagen was significantly increased in diabetic rats( P ＜0.05 ) but showed no changes in GbE group( P ＞0.05). Conclusion GbE can improve diabetic nephropathy by inhibiting the expression of MMP-2 in diabetic Rat.     

2型糖尿病肾病患者血浆MMP-2和MMP-9水平检测的临床意义

目的探讨了2型糖尿病肾病患者血浆MMP-2和MMP-9水平的变化及临床意义。方法采用ELISA法测定了42例糖尿病无肾病和33例糖尿病肾病患者血浆MMP-2和MMP-9水平的变化,并与35例正常健康人作比较。结果2型糖尿病肾病患者血浆MMP-2水平非常显著地高于正常人组(P<0.01),而MMP-9水平则显著地低于正常人组(P<0.01),2型糖尿病肾病组与无肾病组亦有显著性差异(P<0.05)。结论2型糖尿病肾病的发生与发展与血浆MMP-2和MMP-9的水平变化密切相关,具有重要的临床价值。     

MMP-2和MMP-9在Hp阳性的脑梗死患者血清中的表达

目的探讨幽门螺杆菌（Hp）感染阳性的脑梗死（CI）患者血清中MMP-2和MMP-9的表达情况。方法选取2012年1月-2014年3月在菏泽市立医院神经内科住院的CI患者100例,患者均经头颅CT检查、颈动脉造影检查并结合病史确诊,同时选取无CI体征的健康体检者100例为对照组,用ELISA法测定两组的Hp细胞毒素相关基因蛋白（Hp-CagA-IgG）,比较各组的Hp-CagA-IgG阳性率。再把Hp-CagA-IgG阳性的CI患者分为Hp重度感染CI组、Hp轻度感染CI组,把对照组中Hp-CagA-IgG阴性的受试者作为Hp阴性对照组。用ELISA法测定MMP-2、MMP-9,比较各组的MMP-2、MMP-9。结果 CI组的Hp-CagA-IgG阳性率为72.1%,明显高于对照组的44.6%（P〈0.01）。Hp重度感染CI组的MMP-2为（373±126）μg/L、MMP-9为（399±137）μg/L,Hp轻度感染CI组的MMP-2为（267±139）μg/L、MMP-9为（316±132）μg/L,均明显高于Hp阴性对照组（P〈0.01）;Hp重度感染CI组与Hp轻度感CI组的MMP-2、MMP-9比较,差异有统计学意义（P〈0.01）。结论 Hp感染能使CI患者的MMP-2和MMP-9表达量增高,从而使其发生CI的概率增高。     

MMP-2、MMP-9及TIMP-1在颅内动脉瘤中的表达及意义

目的观察基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）和基质金属蛋白酶抑制剂-1（TIMP-1）在颅内动脉瘤中的表达情况,并且与正常颅内动脉的表达相比较,以探讨动脉瘤的发病原因及机制。方法用免疫组织化学方法对31例经手术切除的颅内动脉瘤标本和16例脑外伤病人切除的正常血管中的MMP-2、MMP-9、TIMP-1的表达进行检测和比较,将所得染色标本在光镜下观察,并用医学图像分析系统进行定量分析。结果动脉瘤标本中的MMP-2、MMP-9及TIMP-1明显高于正常血管。结论MMP-2、MMP-9及TIMP-1与颅内动脉瘤密切相关,可能在颅内动脉瘤形成、发展及其破裂过程中发挥重要作用。     

肺腺癌中MMP-9和VEGF的表达及临床意义

目的探讨肺腺癌中MMP-9和VEGF的表达及临床意义。方法对80例肺癌患者的癌组织标本与周围正常组织标本进行免疫组化染色,检测MMP-9和VEGF的表达。结果癌组织中MMP-9表达(+)有63例(78.8%)、VEGF表达(+)有53例(66.3%);癌旁组织中分别有11例(13.8%)、4例(5.0%);比较具有统计学意义(P <0.05)。相关性分析显示,VEGF与MMP-9表达呈正相关(r=0.633,P <0.05)。结论 MMP-9、VEGF在肺腺癌组织中表达上调,且二者表达呈正相关,MMP-9与VEGF可能相互协同或调节对肿瘤的分化、侵袭与转移起作用。     

MMP-2、MMP-9在肺癌中的表达及其与肺癌转移和预后关系的研究

目的探讨基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）在肺癌中的表达水平及其与肺癌转移、肺癌预后的相关联系。方法对80例非小细胞肺癌患者和20例肺良性病变患者进行LSAB法检测其MMP-2和MMP-9的表达水平,并检测其在腺癌、鳞癌和腺鳞混合癌中的表达水平以及在不同分化程度肿瘤中的表达水平,将检测的数据进行对比,分析MMP-2和MMP-9的表达水平与肺癌转移和预后的相关联系。结果 MMP-2、MMP-9在鳞癌中的表达水平最高,而表达水平较低的腺癌和腺鳞混合癌之间差异不大,MMP-2与MMP-9在不同分化程度的肿瘤中表达水平差异不大,MMP-2、MMP-9在肺癌预后方面的表达水平差异具有统计学意义（P〈0.05）。结论 MMP-2与MMP-3在肺癌中的表达水平与肺癌的转移有密切的关系,同时可能成为检测肺癌预后的重要指标。     

丁苯酞对进展性脑梗死患者血清MMP-9、MMP-2及神经功能的影响

目的研究丁苯酞对进展性脑梗死患者血清基质金属蛋白酶(MMP)-9、MMP-2及神经功能的影响。方法选取进展性脑梗死患者93例随机分为对照组和丁苯酞组,另选取45名健康者设为正常组。脑梗死患者均给予常规治疗,丁苯酞组在常规治疗基础上加用丁苯酞注射液100 mL静脉滴注,每日2次,连续用药14 d。采用ELISA法检测患者首诊时、进展后、治疗14 d、随访30 d和90 d的血清MMP-9、MMP-2水平,比较各时点2组美国国立卫生研究院卒中量表(NIHSS)和Barthel指数评定量表评分,比较2组随访90 d时改良Rankin量表(mRS)评分,观察不良反应发生情况。结果进展后丁苯酞组和对照组MMP-9、MMP-2水平显著高于正常组(P <0.05),2组进展后MMP-9和MMP-2水平、NIHSS评分、Bathel指数组间比较均无显著差异(P> 0.05)。丁苯酞组治疗14 d、随访30 d和90 d的MMP-9、MMP-2水平较对照组显著下降(P <0.05);2组治疗14 d、随访30 d和90 d的NIHSS评分均低于进展后、Bathel指数评分高于进展后(P <0.05),且组间有显著差异(P <0.05);丁苯酞组随访90 d的mRS评分显著低于对照组(P <0.05)。2组均无严重不良反应发生。结论丁苯酞可以降低进展性脑梗死患者血清MMP-9、MMP-2水平,改善患者的神经功能,提高生活质量。     

银杏叶提取物对细胞色素P450影响的研究进展

银杏叶提取物(Ginkgo biloba extract,GBE)是目前使用最为广泛的中草药之一。GBE与其他药物合用是否产生药物相互作用得到关注。GBE与其他药物合用,可能通过影响肝药酶的活性发生药物相互作用,其中GBE对肝药酶的诱导或抑制作用的研究较为深入。本综述回顾了近年来报道的关于GBE对细胞色素P450 CYP3A4、CYP2C9、CYP1A2、CYP2C19的影响。     

MMP-9 and MMP-2 regulation in patients undergoing non-oncological and non-vascular elective surgery independent of the use of propofol or sevoflurane

BackgroundThere is debate regarding whether inhaled sevoflurane or intravenous propofol used during anesthesia achieves the best outcome. Propofol has been shown to affect expression of matrix metalloproteinases (MMPs). MMPs are enzymes that play a role in extracellular matrix remodeling, with activity balance disturbances during surgery. The goal of this study was to compare MMP-2/9 concentrations, activity, and tissue inhibitors of metalloproteinases (TIMPs) 1/2 concentrations in blood of who had undergone 2 types of anesthesia: based on volatile sevoflurane and intravenous propofol during non-oncological, non-vascular surgery.Methods39 patients were enrolled into analysis, 20 anesthetized with total intravenous anesthesia with propofol (P), 19 with volatile induction/maintenance of anesthesia with sevoflurane (S). Plasma samples collected before and 24 h after surgery were analyzed for MMP-2/9, and TIMP-1/2 concentrations using ELISAs. Additionally, MMP-2/9 activities were assessed by gelatin zymography.ResultsStudy revealed increased MMP-9 concentration (ELISA) (P:p = 0.011; S:p = 0.001) and activity (zymography) (P:p = 0.004; S:p = 0.008) in both groups 24 h after surgery. We noticed decreased (both groups) MMP-2 concentration (P:p = 0.044; S:p = 0.027) with MMP-2 activity increase (P:p = 0.002; S:p = 0.006) 24 h after surgery. We observed decreased TIMP-1 plasma concentrations (P:p = 0.002; S:p = 0.000) 24 h after procedures, while TIMP-2 plasma levels remain unchanged (P:p = 0.097; S:p = 0.172). There were no differences between concentration and activity of MMPs and TIMPs in regard to anesthetic used. Meperidine administration correlated with lower MMP-9 activity (R=-0.430; p = 0.006).ConclusionsConcluding, neither sevoflurane nor propofol used as anesthetics modulate MMP-2 and MMP-9 concentrations and activities during non-oncological, non-vascular elective surgery. Meperidine seems to decrease MMP-9 activity.     

前列地尔对局灶性脑缺血模型大鼠大脑皮层基质金属蛋白酶2和基质金属蛋白酶9表达的影响

目的:探讨前列地尔对局灶性脑缺血模型大鼠大脑皮层基质金属蛋白酶(MMP)2和MMP-9表达的影响。方法:取SD大鼠随机分为假手术组、模型组、阳性对照(尼莫地平1 mg.kg-1)组和前列地尔低、中、高剂量(1.25、2.50、5.00μg.kg-1)组,每组5只,连续给予相应药物6 d,每日1次,末次给药后建立局灶性脑缺血模型,于大鼠清醒后进行神经功能缺损评分,缺血24 h后检测各组大鼠大脑皮层MMP-2、MMP-9的表达情况。结果:与假手术组比较,模型组神经功能缺损评分明显更高,MMP-2、MMP-9表达明显升高(P<0.05);与模型组比较,阳性对照组和前列地尔中、高剂量组神经功能缺损评分明显较低,MMP-2、MMP-9表达明显降低(P<0.05)。结论:前列地尔预处理对局灶性脑缺血模型大鼠具有神经保护作用,其机制可能与抑制大脑皮层MMP-2、MMP-9的表达有关。     

银杏叶提取物及其不同成分对CYP3A4活性的影响

目的:研究银杏叶提取物及其中2种主要活性物质黄酮和内酯对人体内CYP3A4酶活性的影响。方法:构建了可用于体外高通量检测基于PXR诱导的CYP3A4系统,通过细胞培养实验,化学发光检测仪检测银杏叶不同组分对CYP3A4的激活水平。采用反相高效液相色谱法测定银杏叶不同组分对细胞内尼卡地平代谢的影响。结果:高通量检测系统检测表明,银杏叶提取物对体内的CYP3A4酶表达具有显著的激活作用。进一步研究证实银杏叶提取物的两类主要活性物质黄酮和内酯呈剂量的方式激活CYP3A4的表达。银杏叶内酯明显加速尼卡地平的代谢速率,而银杏叶黄酮则降低细胞内尼卡地平的降解速率。结论:银杏叶提取物及其主要活性成分黄酮和内酯能显著提高CYP3A4的活性,内酯能提高CYP3A4代谢尼卡地平的能力,而黄酮则可能由于药物相互作用的原因,抑制了CYP3A4酶活性,降低其代谢尼卡地平的能力。     

Egb761对哮喘模型大鼠MMP-9及TIMP-1表达的影响和对气道重构的干预研究

目的:研究银杏叶提取物(Egb761)对哮喘大鼠气道上皮细胞基质金属蛋白酶-9(MMP-9)及其抑制剂-1(TIMP-1)表达的影响和对气道重构的干预作用。方法:40只大鼠随机均分为4组,即正常对照、哮喘模型、地塞米松及Egb761组,以吸入卵蛋白复制大鼠哮喘模型,用免疫组化技术结合计算机病理图像分析技术,测定各组大鼠气道形态学参数和气道上皮细胞MMP-9及TIMP-1表达的相对含量。结果:哮喘模型组大鼠气道壁的总厚度及内壁厚度和平滑肌层的厚度均显著高于正常对照、地塞米松和Egb761组(P<0.05);哮喘模型组MMP-9及TIMP-1表达量也显著高于上述3组(P<0.01);哮喘模型组MMP-9与TIMP-1的比例显著失衡。结论:少量多次的卵蛋白吸入可以导致大鼠气道重构的发生,MMP-9及TIMP-1在气道重构中发挥着重要作用,Egb761对哮喘模型大鼠的气道重构有干预作用。     

卡维地洛对慢性充血性心力衰竭患者血清基质金属蛋白酶-2、9、10水平的影响及疗效观察

探讨卡维地洛对慢性充血性心力衰竭（CHF）患者血清基质金属蛋白酶-2、9、10水平的影响及其疗效。方法：76例CHF患者随机分为观察组与对照组。两组患者均予以强心（地高辛）、利尿（噻嗪类）和扩张血管（硝酸酯类）等常规治疗。观察组在此基础上加用卡维地洛片治疗,连用6个月。观察两组患者治疗前和治疗6个月后患者血清MMP-2、9、10水平变化,并进行疗效及安全性观察。结果：治疗6个月后,两组血清MMP-2、9、10水平均有明显下降（P〈0．05）,且观察组各指标较对照组下降更显著（P〈0．05）;同时观察组总有效率为94．74％,明显高于对照组的78．75％（P〈0．05）。结论：卡维地洛治疗CHF具有良好的疗效和安全性,作用机制可能与降低血清MMP-2、9、10水平密切相关。     

银杏叶提取物对脑缺血再灌注大鼠的保护作用

目的探讨银杏叶提取物(GbE)对缺血性脑卒中神经元保护作用机制。方法SD大鼠60只随机分为假手术组、再灌注组及银杏叶组。脑缺血再灌注损伤模型以脑中动脉建立。银杏叶组在术前给予口服GbE,再灌注组给予生理盐水,用免疫组化染色检测海马CA1区凋亡细胞数。结果再灌注组各时段的细胞凋亡数明显高于假手术组(P<0.05),银杏叶组各时段的细胞凋亡数明显低于再灌注组(P<0.05)。结论银杏叶可能对海马神经元有保护作用。     

Effects of Ginkgo biloba on alertness and chemosensory function in healthy adults

Ginkgo biloba is reported to enhance cognitive function in patients with selected neural disorders. Its effects in healthy, young adults are less well characterized. This work explored whether Ginkgo biloba could ameliorate decrements in alertness post-prandially and/or enhance chemosensory function. Both are functions that could be influenced by enhanced cerebral blood flow and neuronal metabolism, reported properties of the compound. A double-blind placebo-controlled study was conducted with 19 males and 20 females with a mean age of 23.6 +/- 5.4 years and mean weight of 70.0 +/- 1.9 kg. Participants were supplemented for 13 weeks with either Ginkgo biloba (mean dose 184.5 mg/d (range 130-234 mg/d)) or placebo and administered various alertness, performance, affective state and chemosensory tests at weeks 1, 5, 9 and 13. Participants did experience the post-prandial affective state decrement (i.e. post-lunch dip), but not the performance decrement. Performance on the chemosensory tests improved over the 13-week study. However, Ginkgo biloba was ineffective at alleviating the symptoms of the post-lunch dip or at enhancing taste and smell function.